The leukotrienes constitute a group of locally acting hormones, produced in living systems from arachidonic acid. The major leukotrienes are Leukotriene B4 (abbreviated at LTB.sub.4), LTC.sub.4, LTD.sub.4, and LTE.sub.4. The biosynthesis of these leukotrienes begins with the action of the enzyme 5-lipoxygenase on arachidonic acid to produce the epoxide known as Leukotriene A.sub.4 (LTA.sub.4), which is converted to the other leukotrienes by subsequent enzymatic steps. Further details of the biosynthesis as well as the metabolism of the leukotrienes are to be is found in the book Leukotrienes and Lipoxygenases, ed. J. Rokach, Elsevier, Amsterdam (1989). The actions of the leukotrienes in living systems and their contribution to various diseases states are also discussed in the book by Rokach.
Several classes of compounds exhibit the ability to inhibit the biosynthesis of leukotrienes in mammals, especially humans.
EP 181,568 describes a series of compounds of the general formula: EQU Ar.sub.1 --X--Ar--Z--(R).sub.n
which differ from the present invention in not having a cycloalkyl or phenyl substituent (R) attached directly to the alkylene chain Z and in not having the Q substituent in the preferred embodiment of the present invention attached by a sulfur atom to the alkylene chain.
U.S. Pat. No. 4,631,287 contains compounds of the formula: EQU (R.sub.1)(R.sub.2)Ar--Z--M--Ar.sub.1 (R.sub.3)(R.sub.4)
which differ from the present invention in that the R.sub.3 and R.sub.4 substituents which contain a carboxy group (corresponding to the Q substituent of the present invention) are attached directly to Ar.sub.1 by an oxygen atom. Further, when they contain an aryl group, it is either attached directly to Ar.sub.1 or is attached through an oxygen atom. Furthermore, R.sub.3 or R.sub.4 do not simultaneously include the Q substituent of the present invention and the cycloalkyl or phenyl substituent of the present invention.
EP 200,101 and Australian Patent application 56398/86 disclose compounds of the formula: EQU (R.sub.1)(R.sub.2)Ar--Z--M--Z.sub.1 --Ar.sub.1 (R.sub.3)(Z.sub.2 --Y--Z.sub.3 -R.sub.4)
which differ from the compounds of the present invention in that the substituent unit (Z.sub.2 --Y--Z.sub.3 --R.sub.4) does not simultaneously contain the cycloalkyl or phenyl and Q substituents of the present invention.
W0 87/05510 discloses compounds of the general formula: ##STR2## which differ from the compounds of the present invention in that they contain the heterocyclic tetrazole moiety which is absent from the present compounds, and in that the phenyl group present in the R.sub.2 and R.sub.3 substituents is unsubstituted.
Zamboni et al. in U.S. Pat. No. 5,102,881 describe the following compounds as inhibitors of leukotriene biosynthesis: ##STR3##